Rheumatoid factors (RF) are antibodies to the Fc fragments of IgG and they are the major autoantibodies of pathological significance in rheumatoid arthritis (RA), a major crippling disorder. Previous studies with RF isolated from patients' plasma and synovial fluid as well as cultured cells have revealed the complexity of RF reactivities. The definitive demonstration of a population of RF unique to RA patients has not been feasible although ample suggestive data have been accumulated. Recently, we have established multiple RF secreting cell lines by Epstein-Barr viral transformation from peripheral blood of patients with RA, systemic lupus erythematosus (SLE), Alzheimer's disease (AD) and normals of various ages as well as from certain cord blood. Preliminary data indicate some of the RF from RA cell lines may have specificities of considerable interest. In the present proposal, we intend to establish additional RF secreting EBV transformed cell lines from circulatory B cells and synovial B cells of RA patients. The specificities of these RF secreted by RA cell lines will be determined by their reactivity with rabbit IgG, autologous IgG, IgG subclass proteins and their fragments. Both IgM and IgG RF will be studied. These RF will be compared with those obtained from patients and normals without RA. Serological and molecular biology techniques will be used to determine VH and VL region utilization by these RF. Major cross-reactive idiotypes of these cell line secreted RF will be determined. Systems of analyses will be developed to determine whether these cross-reactive idiotypes are represented in RF isolated from RA patients' plasma and synovial fluid. These studies will identify RF of unique specificity in RA and provide useful information as to the cellular and molecular origin of RF formation.